Conformational Heterogeneity of Arylamine-Modified DNA: 19F NMR evidence

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One- and two-dimensional 19F NMR spectroscopy was used to investigate the conformational heterogeneity of two arylamine-modified DNA duplexes, d[CTTCTTG*ACCTC]·d[GAGGTCAAGAAG], in which G* is either N-(deoxyguanosin- 8-yl)-4'-fluoro-4-aminobiphenyl (dG-C8-FABP) (I) or N-(deoxyguanosin-8-yl)- 7-fluoro-2-aminofluorene (dG-C8-FAF) (II). The 19F NMR spectrum of I showed a single peak, while that of II revealed two prominent signals with a 55:45 ratio, in good agreement with previous 1H NMR results (Cho et al. Biochemistry 1992, 31, 9587-9602; 1994, 33, 1373-1384). Slow interconversion between the two conformations of II was established by temperature-dependent two-dimensional 19F NMR chemical exchange spectra. On the basis of magnetic anisotropy effects and isotopic solvent-induced shifts, the 19F signals at -117.31 and -118.09 ppm in the 19F NMR spectrum of 11 were assigned to a relatively undisturbed 'B-type' conformer and a highly perturbed 'stacked' conformer, respectively. Analysis of the temperature dependent (5-40°C) line shapes by computer simulation yielded an interconversion barrier (ΔG((+))) of 14.0 kcal/mol with a chemical exchange time of 2 ms at 30°C. This new 19F approach should be very useful in investigating the sequence-dependent conformational heterogeneity of arylamine-modified DNA.

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Journal of the American Chemical Society